SND-117, a sinomenine bivalent alleviates type II collagen-induced arthritis in mice.

Abstract

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that affects about 1% of the population worldwide. RA is mainly manifested by persistent synovitis and progressive joint destruction. The aim of the present study was to examine the anti-arthritis effects of SND-117, a sinomenine bivalent that is obtained from the structure modification of a clinically available anti-RA drug, sinomenine. The arthritis model (CIA) was established by immunizing DBA/1 mice with type II collagen, and the arthritis scores including inflammation, joint destruction and bone erosion were assessed after booster immunization for 3weeks. The levels of cytokines such as IL-1β, IL-6 and TNF-α were analyzed by quantitative PCR and ELISA. The TNF-α induced NF-κB activation in fibroblast-like synovial cells (FLSCs) was analyzed by Western blot. SND-117 significantly relieved the inflammatory symptoms of collagen-induced arthritis, reduced bone erosion and joint destruction in CIA mice. The serum levels of IL-1β, IL-6 and TNF-α of CIA mice were markedly decreased by SND-117. SND-117 also strongly inhibited the phosphorylation and nuclear translocation of NF-κB p65 in FLSCs upon TNF-α stimulation. These data demonstrated that SND-117 could effectively block the pathogenesis of collagen-induced arthritis in CIA mice via inhibition of NF-κB signaling, and might provide potential clinic benefits in rheumatoid arthritis management.

• Authors: Yu-Ren Zhou, Yang Zhao, Bei-Hua Bao, Jian-Xin Li
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 26 Issue 2 Pg. 423-31 (Jun 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25887268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antirheumatic Agents
• Collagen Type II
• Cytokines
• Inflammation Mediators
• Morphinans
• NF-kappa B
• sinomenine

Topics

• Animals
• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (drug therapy, immunology)
• Bone and Bones (drug effects, pathology)
• Collagen Type II (immunology)
• Cytokines (blood)
• Disease Models, Animal
• Fibroblasts (physiology)
• Humans
• Immunization, Secondary
• Inflammation Mediators (blood)
• Male
• Mice
• Mice, Inbred DBA
• Morphinans (administration & dosage, chemistry)
• NF-kappa B (metabolism)
• Sinomenium
• Synovitis (chemically induced, drug therapy)